title: Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes.
abstract: BACKGROUND
  Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria.
  
  
  METHODS
  In a randomized, double-blind, multicenter, controlled trial, we assigned 4447 patients with type 2 diabetes to receive olmesartan (at a dose of 40 mg once daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs (except angiotensin-converting-enzyme inhibitors or ARBs) were used as needed to lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time to the first onset of microalbuminuria. The times to the onset of renal and cardiovascular events were analyzed as secondary end points.
  
  
  RESULTS
  The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P=0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events--81 of 2232 patients (3.6%) as compared with 91 of 2215 patients (4.1%) (P=0.37)--but a greater number had fatal cardiovascular events--15 patients (0.7%) as compared with 3 patients (0.1%) (P=0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P=0.02).
  
  
  CONCLUSIONS
  Olmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern. (Funded by Daiichi Sankyo; ClinicalTrials.gov number, NCT00185159.).
authors.affiliation: Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany. haller.hermann@mh-hannover.de
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Joseph L
authors.initials: JL
authors.lastname: Izzo
authors.forename: Andrzej
authors.initials: A
authors.lastname: Januszewicz
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Katayama
authors.forename: Jan
authors.initials: J
authors.lastname: Menne
authors.forename: Albert
authors.initials: A
authors.lastname: Mimran
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Luis M
authors.initials: LM
authors.lastname: Ruilope
authors.forename: Lars C
authors.initials: LC
authors.lastname: Rump
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Viberti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000453:epidemiology / Q000517:prevention & control*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000401:mortality; D003327:Coronary Disease / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan